The extracellular matrix in solid tumor immunotherapy | JoVE Visualize

Area of Science:

Immunology
Biomaterials Science
Cancer Biology

Background:

The tumor extracellular matrix (ECM) significantly influences the efficacy of cytotoxic lymphocytes, including CD8+ T cells and natural killer (NK) cells, in solid tumors.
The ECM presents physical barriers, impeding immune cell motility, and directly modifies immune cell phenotypes and functions.
It also indirectly affects crucial interactions between cytotoxic lymphocytes and cancer cells at the immunological synapse.

Purpose of the Study:

To highlight the critical role of the tumor extracellular matrix (ECM) in modulating antitumor immunity mediated by CD8+ T cells and NK cells.
To emphasize the necessity of considering the intricate interplay between cytotoxic lymphocytes, cancer cells, and the tumor ECM for developing effective solid tumor immunotherapies.
To underscore the value of bioengineering tools that mimic tumor ECM characteristics for fundamental research and translational applications.

Main Methods:

Review and synthesis of existing literature on the tumor ECM's impact on cytotoxic lymphocyte function.
Discussion of the physical and functional alterations induced by the ECM on T cells and NK cells.
Exploration of novel bioengineering approaches, such as 3D ECM models and microfluidics, for studying these interactions.

Main Results:

The tumor ECM restricts the motility of CD8+ T cells and NK cells, creating physical barriers within the tumor microenvironment.
The ECM directly alters the phenotype and function of these cytotoxic lymphocytes.
The ECM indirectly influences the formation and efficacy of immunological synapses between immune cells and cancer cells.

Conclusions:

Effective solid tumor immunotherapy strategies must integrate an understanding of the complex ternary interactions involving cytotoxic lymphocytes, cancer cells, and the tumor ECM.
Bioengineering tools that replicate key features of the tumor ECM are essential for advancing both fundamental research and translational applications in cancer immunotherapy.
Further investigation into these interactions using advanced models will facilitate the development of more potent and targeted immunotherapies.